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Human MxB Inhibits the Replication of Hepatitis C Virus
- Source :
- Journal of Virology. 93
- Publication Year :
- 2019
- Publisher :
- American Society for Microbiology, 2019.
-
Abstract
- Type I interferon (IFN) inhibits viruses by inducing the expression of antiviral proteins. The IFN-induced myxovirus resistance B (MxB) protein has been reported to inhibit a limited number of viruses, including HIV-1 and herpesviruses, but its antiviral coverage remains to be explored further. Here we show that MxB interferes with RNA replication of hepatitis C virus (HCV) and significantly inhibits viral replication in a cyclophilin A (CypA)-dependent manner. Our data further show that MxB interacts with the HCV protein NS5A, thereby impairing NS5A interaction with CypA and NS5A localization to the endoplasmic reticulum, two events essential for HCV RNA replication. Interestingly, we found that MxB significantly inhibits two additional CypA-dependent viruses of the Flaviviridae family, namely, Japanese encephalitis virus and dengue virus, suggesting a potential link between virus dependence on CypA and virus susceptibility to MxB inhibition. Collectively, these data have identified MxB as a key factor behind IFN-mediated suppression of HCV infection, and they suggest that other CypA-dependent viruses may also be subjected to MxB restriction. IMPORTANCE Viruses of the Flaviviridae family cause major illness and death around the world and thus pose a great threat to human health. Here we show that IFN-inducible MxB restricts several members of the Flaviviridae, including HCV, Japanese encephalitis virus, and dengue virus. This finding not only suggests an active role of MxB in combating these major pathogenic human viruses but also significantly expands the antiviral spectrum of MxB. Our study further strengthens the link between virus dependence on CypA and susceptibility to MxB restriction and also suggests that MxB may employ a common mechanism to inhibit different viruses. Elucidating the antiviral functions of MxB advances our understanding of IFN-mediated host antiviral defense and may open new avenues to the development of novel antiviral therapeutics.
- Subjects :
- Myxovirus Resistance Proteins
viruses
Hepatitis C virus
Immunology
Cypa
Hepacivirus
Viral Nonstructural Proteins
Biology
Dengue virus
Endoplasmic Reticulum
Virus Replication
medicine.disease_cause
Microbiology
Virus
Cell Line
03 medical and health sciences
Flaviviridae
Interferon
Virology
Chlorocebus aethiops
medicine
Animals
Humans
NS5A
Vero Cells
030304 developmental biology
0303 health sciences
030306 microbiology
biology.organism_classification
Virus-Cell Interactions
3. Good health
HEK293 Cells
Viral replication
Gene Knockdown Techniques
Insect Science
Cyclosporine
Interferons
Cyclophilin A
Protein Binding
medicine.drug
Subjects
Details
- ISSN :
- 10985514 and 0022538X
- Volume :
- 93
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....362ce59b0577f5cad140bad88e654ba1